The effect of doxorubicin (DOX) used in combination with a low dose (10(-7) M) of all-trans-retinoic acid (tRA) was tested on MCF-7 breast carcinoma cell line. Both drugs are able to inhibit cell proliferation in these cells in a dose-dependent way. The combined treatment with DOX and tRA was more effective in inhibiting cell growth than each of the two compounds alone. This was evidenced in the following experimental conditions: pre-treatments with tRA, for 72 h or 18 h, before DOX incubation; post-treatment with tRA for 18 h after DOX incubation. A consistent synergism was reached by 72 h pre-treatment with tRA and also with brief pre- and post-treatments, but only if tRA was also present during DOX incubation (co-treatments). The mechanisms involved in this interaction between chemotherapeutics and differentiating agents are as yet unclear and should be evaluated further.